PTEN attenuates PIP3/Akt signaling in the cochlea of the aging CBA/J mouse
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Updated: Jun 20, 2026
Evaluation of Planar-Cell-Polarity Phenotypes in Ciliopathy Mouse Mutant Cochlea
Published on: February 21, 2016
Su-Hua Sha1, Fu-Quan Chen, Jochen Schacht
1Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI 48109, USA. shasha@umich.edu
Abstract:
We have previously reported the activation of cell death pathways in the sensory cells of the aging cochlea. Here we investigate age-associated changes in survival mechanisms focusing on phosphatidylinositol 3,4,5-trisphosphate (PIP(3))/Akt signaling. The animal model is the CBA/J mouse of 18 months of age prior to the onset of major functional loss (ABR thresholds, 26+/-8 dB SPL) which is compared to young animals of 3 months of age (ABR thresholds, 19+/-7 dB SPL). Immunostaining on cochlear cryosections revealed a wide-spread distribution of PIP(3) in the cochlea which was markedly attenuated in old animals in inner and outer hair cells, Deiters cells and pillar cells. Protein levels of the lipid phosphatase PTEN which regulates PIP(3) increased in those cells with aging while its mRNA did not, suggesting an age-related reduction of PTEN degradation. Furthermore, staining intensity of phosphorylated PTEN (ser380) and its nuclear localization increased. Consistent with a reduction of PIP(3), the phosphorylation of the downstream target Akt at threonine 308 significantly decreased in outer hair cells. The results suggest a decline of the survival capacity of aging outer hair cells due to a decrease in PIP(3)/Akt signaling caused by an increase of PTEN.
Insights
Aging cochlea sensory cells show reduced survival pathways. This study reveals decreased phosphatidylinositol (3,4,5)-trisphosphate (PIP(3))/Akt signaling due to increased PTEN, impacting hearing health.
Area of Science:
- Otolaryngology
- Cell Biology
- Aging Research
Background:
- Previous work identified cell death pathway activation in aging cochlear sensory cells.
- This study focuses on age-associated changes in survival mechanisms, specifically the phosphatidylinositol (3,4,5)-trisphosphate (PIP(3))/Akt signaling pathway.
Purpose of the Study:
- To investigate age-related alterations in PIP(3)/Akt signaling in the CBA/J mouse cochlea.
- To determine the role of PTEN in modulating PIP(3) levels during aging.
Main Methods:
- Comparative analysis of young (3 months) and aged (18 months) CBA/J mice.
- Immunostaining of cochlear cryosections to assess PIP(3) and phosphorylated PTEN distribution and levels.
- Analysis of PTEN and Akt phosphorylation (p-Akt) in cochlear sensory cells.
Main Results:
- PIP(3) levels were significantly attenuated in aged cochlear cells (inner/outer hair cells, Deiters cells, pillar cells).
- Protein levels of PTEN increased with age, while mRNA levels remained unchanged, suggesting reduced PTEN degradation.
- Increased PTEN phosphorylation and nuclear localization were observed in aged cochlear cells.
- Downstream Akt phosphorylation (at Thr308) decreased in outer hair cells of aged mice.
Conclusions:
- Aging leads to a decline in PIP(3)/Akt survival signaling in cochlear sensory cells.
- Increased PTEN activity, likely due to reduced degradation, contributes to the decrease in PIP(3) and subsequent impaired cell survival.
- These findings highlight a potential mechanism for age-related hearing dysfunction.
